Methods and compositions for the treatment of benign prostatic hypertrophy

ABSTRACT

This invention relates to a composition for use in treating benign prostatic hyperplasia including a saw palmetto extract provided in an oral controlled release formulation which allows release of active ingredients in the intestinal tract and which allows the maintenance of therapeutic levels of active agents in the bloodstream for prolonged periods of time. This invention also relates to a composition for improving the efficacy of a saw palmetto extract, a method of treating benign prostatic hypertrophy, and a method of improving the efficacy of a saw palmetto extract treatment.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] This invention relates to a composition for use in treatingbenign prostatic hyperplasia, which comprises saw palmetto extractcontained in a controlled delivery system. The composition is preferablyadministered orally, uses a controlled delivery system to provide atargeted, extended release of the saw palmetto extract into thebloodstream.

[0003] 2. Related Art

[0004] Many men over the age of fifty commonly experience a conditionknown as benign prostatic hyperplasia, or BPH. BPH affects as much as40% of the male population over the age of seventy. The condition iscommonly recognized as a swelling of the prostate gland. This problemgradually manifests itself in the form of a) frequent urination, b)small discharge volumes and “dribbling”, and c) unsatisfying bladderevacuations. Waking up to urinate once or more each night is a typicalsign of this problem. BPH is a chronic condition that tends to graduallyworsen with age.

[0005] The increased incidence of BPH in older men may be due to thefact that as men age, testosterone levels tend to decline and estrogenlevels rise. In the process, testosterone metabolism takes a differentpathway, and testosterone is converted to dihydrotestosterone (DHT), apotent male hormone that causes prostate enlargement. The actions of DHTcan be limited by restricting the enzymatic production of DHT fromtestosterone and/or blocking the direct pharmacological action of DHT atthe receptor level. Current therapies for BPH focus on limiting theactions of DHT, and include: pharmaceutical intervention with5-α-reductase inhibitors such as finasteride (Proscar®); pharmacologicalintervention with α-adrenergic blockers, such as terazosin HCl(Hytrin®), and doxazosin mesylate (Cardura®); prostatectomy; andadministration of saw palmetto extract.

[0006] Extract of the saw palmetto berry (Serenoa repens) has beendemonstrated to be effective in treating the symptoms of BPH in numerousclinical trials, including a number of double-blind studies. Forexample, a meta-analysis of existing clinical evidence for the efficacyand safety of the use of saw palmetto extract to treat BPH was publishedby Witt et al., JAMA (1999), 18:1604-1609. This analysis concludes thatsaw palmetto extract is effective in treating BPH, as compared withProscar®.

[0007] Saw palmetto extracts have been used in various products intendedto treat BPH. For example, in U.S. Pat. No. 5,543,146, a composition fordietary supplements including pumpkin seed, extracts of saw palmetto,and various other components is disclosed. This composition is used as adietary supplement for alleviating the symptoms associated withenlargement of the prostate gland.

[0008] In U.S. Pat. No. 6,200,573, which relates to a method formanaging BPH, a combination therapy of an α-adrenergic antagonist suchas terazosin and a phyto-therapeutic agent such as saw palmetto extractis disclosed. The active ingredients may be administered in combinationwith diluents and other carriers, for oral or parental administration,or may be delivered by any conventional delivery system. It is alsodisclosed that the active ingredients may also be formulated intoonce-a-day or longer sustained release compositions, although noguidance is given in this regard.

[0009] U.S. Pat. No. 6,039,950 relates to a method of makingmedicinally-useful saw palmetto materials in pharmaceutically acceptableforms. It discloses compositional and activity fingerprints for use inprocessing saw palmetto materials to produce compositions suitable foruse in clinical or veterinary settings to treat various conditions. Themethod involves measuring the bioactivity of a sample of saw palmettoextract using an androgen receptor binding inhibition assay.

[0010] U.S. Pat. No. 6,197,309 relates to a composition for preventingor improving disorders of the prostate gland. The composition preferablyincludes therapeutically effective amounts of vitamin C, vitamin B-6,vitamin E, zinc, glycine, L-alanine, glutamic acid, saw palmettoextract, Pygeum extract, pumpkin seed, stinging nettle, Echinacea,garlic, ginkgo biloba, and selenium.

[0011] Finally, U.S. Pat. No. 6,019,976 relates to therapeuticformulations containing saw palmetto extract, vitamin B-6, vitamin B-3,zinc, and L-arginine. The formulations are used to treat male patternbaldness by topical application to the hair. The formulations may alsobe provided in the form of a drink, or in a capsule formed of gelatinand glycerin.

[0012] Other compositions have been focused on treating smooth musclespasms, such as those that occur in the bladder, prostate, and urethra,including the compositions disclosed in U.S. Pat. No. 4,725,593. Suchcompositions may be administered orally, by intravenous injection, or bytopical application.

[0013] None of the methods or compositions discussed above addresstreating benign prostatic hyperplasia by administering saw palmettoextract in a controlled delivery vehicle for extended, targeted releaseof the extract in the small intestine. Further, none of the methods orcompositions discussed above address a method of improving the deliveryof saw palmetto extract by providing the extract in the form of an oraladministration vehicle comprising a controlled release system.

SUMMARY OF THE INVENTION

[0014] This invention relates to a method for improving the efficacy andconvenience of oral saw palmetto therapy in the treatment of benignprostatic hyperplasia, or BPH, through the use of a controlled releaseformulation. The controlled release formulation allows the targetedrelease of the extract in a specific part or parts of the digestivesystem, and the extended release of the extract over the course ofdigestion. The targeted release is designed to deliver the active agent,extract of the saw palmetto berry (i.e., especially the phytosterolscontained therein), to the portions of the digestive tract most suitedfor its absorption. The extended release is also designed to deliver theextract over a period of time, determined by routine methods, to be ofthe optimum length for this type of therapy. The controlled release sawpalmetto extract composition of this invention improves theeffectiveness of saw palmetto therapy for BPH by optimizing theabsorption of the extract within the digestive tract, maintaining atherapeutic level of the active agent in the bloodstream for asufficient length of time so as to reduce the dosages and the frequency(i.e., preferably once a day). The composition of this invention alsoimproves the efficiency of saw palmetto therapy by combining the sawpalmetto extract with one or more additional antispasmodic agents.

[0015] The methods and compositions of this invention address the needin the art for a more effective and convenient BPH treatment, as setforth above. More specifically, one aspect of this invention provides acomposition for use in treating benign prostatic hyperplasia andcomprises a saw palmetto extract provided in a controlled release oraldelivery formulation, which comprises, for example, a coating formedfrom a material impervious to acidic conditions in the stomach that issoluble in the duodenum and small intestine.

[0016] According to another aspect of this invention, a composition forimproving the effectiveness of saw palmetto extract therapy comprises asaw palmetto extract provided in a controlled release oral formulation,which comprises a coating formed from a material impervious to acidicconditions in the stomach that is soluble in the duodenum and smallintestine.

[0017] According to an additional aspect of this invention, acomposition for improving the efficacy of saw palmetto extractscomprises an effective amount of a saw palmetto extract, and one or moreantispasmodic compounds (compounds which reduce smooth musclecontractions) selected from the group consisting but not limited toextracts or tinctures of Belladonna alkaloid, Choleus Forskholi,European Goldenrod, Peppermint, and Passion Fruit seed.

[0018] A preferred composition of the present invention comprises atwo-part hard shell capsule that encases a matrix holding from about 100mg to about 1 g of saw palmetto extract, and more preferably about 320mg of the extract.

[0019] According to a further aspect of this invention, an improvementin an orally-administered controlled-release composition comprising sawpalmetto extract comprises a compound that minimizes smooth musclecontractions, the controlled release system being selected from thegroup consisting of microencapsulation in coatings of variablethickness, each with a different dissolution pattern; encapsulation in amaterial matrix that dissolves slowly in the neutral environment of theduodenum and small intestine; and binding with bioadhesives that adhereto the wall of the small intestine.

[0020] According to yet another aspect of this invention, a method oftreating benign prostatic hyperplasia comprises the step ofadministering a therapeutically effective amount of a saw palmettoextract provided in a controlled release oral formulation that includesa coating formed from a material impervious to acidic conditions in thestomach, but which is soluble in the duodenum and small intestine.

[0021] According to an additional aspect of this invention, a method ofimproving the efficacy of saw palmetto extract treatment comprises thesteps of providing a therapeutically effective amount of a saw palmettoextract in an oral formulation, and encapsulating the saw palmettoextract in a coating formed from a material impervious to acidicconditions in the stomach that is soluble in the duodenum and smallintestine.

[0022] According to a further aspect of this invention, a method forimproving the efficacy of saw palmetto extract treatment comprises thesteps of providing a therapeutically effective amount of a saw palmettoextract, and further providing one or more antispasmodic compoundsselected from the group consisting of extracts or tinctures ofBelladonna alkaloid, Choleus Forskholi, European Goldenrod, Peppermint,and Passion Fruit seed.

[0023] It will be apparent to those skilled in the art that only thepreferred embodiments have been described by way of exemplification, andthat there are various modifications which fall within the scope of thisinvention. These and other aspects of the invention will be discussed ingreater detail below.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] While the present invention will be described primarily withrespect to a method and composition for treating BPH, and improving thedelivery of saw palmetto extract, it is to be understood that thefeatures thereof will find applicability to other areas, such as thetreatment of other disorders related to increased levels of DHT, such asmale pattern baldness. The term “benign prostatic hyperplasia” or “BPH”as used herein is meant to refer to the condition characterized byswelling of the prostate gland, and the accompanying frequent urinationand small discharge volumes. The term “saw palmetto extract” as usedherein is meant to refer to the extract of the saw palmetto plant(Serenoa repens) in the form of an oil, a water-soluble concentrate, oran alcohol-soluble concentrate of that plant. The terms “extendedrelease”, “targeted release”, and “controlled release” as used hereinare meant to refer to a delivery system or formulation for oraldelivery, characterized, for example, by a coating used to control therate and/or location of the release of the active ingredients of theoral formulation, or by an enteric coating.

[0025] The saw palmetto extract according to this invention ispreferably in the form of an oil, is preferably derived from the sawpalmetto berry, and may be metabolized much like any other fat or oil.Is likely that the triglycerides that make up the oil are digested bygastric and intestinal lipases and bile acids into free fatty acids andmonoglycerides, which are a suitable form for absorption. Thesemonoglycerides form micelles that further solubilize the fatty acids,and the micelles are absorbed by the mucosal cells of the smallintestine. However, fatty acids are not likely to be the therapeuticallyactive components in saw palmetto extract's treatment of BPH. Thecompounds in saw palmetto extract hypothesized to mediate BPH therapyare the phytosterols, or plant hormones. The phytosterols may also uselipids as a carrier, and this may be the means by which they areabsorbed by the mucosal cells of the small intestine.

[0026] Through use of extended release technologies, the presentinvention allows the maintenance of an extended release of the activeingredients in the duodenum and small intestine for between 3 and 24hours. Such technologies allow extension of the theoretical ceiling fordelivery of the active ingredient beyond the typical transit timethrough this region of the gastrointestinal tract.

[0027] While not intending the invention to be limited by specificmechanisms, the pharmacological effect of saw palmetto extract ishypothesized to occur by one or more of the following four mechanisms ofaction, which are presented by way of illustration, and not limitation.

[0028] 1. Blockage of the Enzyme 5-α-reductase

[0029] This enzyme governs the conversion of testosterone to DHT, whichis a potent hormone that causes the prostate to increase in mass. InBPH, the increased tissue mass is benign; however, the urologicalcomplications are severe enough that intervention is usually eventuallyrequired. DHT is also known to be involved in male pattern baldness. Infact, finasteride (Propecia®) a 5-α-reductase inhibitor, is prescribedfor this condition. DHT has also been implicated in the dermatologicalhormone-related problems of adolescent acne. It appears thatphytosterols may block the binding of testosterone to 5-α-reductase bycompeting for the same binding site on the 5-α-reductase enzyme.

[0030] 2. Direct Blockage of DHT Receptors

[0031] In addition to inhibiting DHT synthesis, saw palmetto extractappears to block the androgen receptors to which DHT binds and throughwhich it exerts its biological effects, including prostate enlargement.Finasteride has not been demonstrated to have this direct andindependent action on androgen receptors.

[0032] 3. Blockage of Adrenergic Receptors

[0033] Evidence suggests that saw palmetto extract also blocksα-adrenergic receptors, which are well-recognized pharmacologicaltargets for the treatment of BPH. This mechanism provides relief to BPHpatients via smooth muscle relaxation in the bladder neck, prostatecapsule, and prostatic urethra, resulting in a number of beneficialurological effects. However, the use of selective α-adrenergicpharmaceutically pure compounds, such as Terazosin®, which possesses ahigh side effect profile, is limited by unwanted cardiovascular effects.

[0034] 4. Anti-inflammatory Activity

[0035] Increasing evidence suggests that phytosterols haveanti-inflammatory properties with respect to the prostate gland. Extractof saw palmetto has been shown to inhibit cyclooxygenase and5-lipoxygenase, enzymes which are involved in the inflammatory process.Beneficial effects of phytosterols include the normalization ofcapillary permeability. This provide clinical benefits to BPH patientsbecause the prostate often becomes inflamed as it enlarges.

[0036] This invention relates to an orally delivered capsule, pill, orother oral dosage form that improves the efficacy of saw palmettotreatment for BPH by controlling and targeting the release of the activeingredient in the receiving membranes of the small intestine, andcontinuing an extended release of the extract over the course of itstravel through the duodenum and small intestine. The targeted release ofthe extract into the small intestine is achieved by coating the pill orcapsule with a material impervious to the acidic environment of thestomach, which has a pH of approximately 2 to 3 and which provides acontrolled extended release of the extract and which avoids the spikeand collapse phenomenon seen with standard gel cap or tablet release.The coating of the pill should also be soluble in the more neutralenvironment of the duodenum and small intestine. This controlled releaseprevents the active ingredient from being degraded due to exposure tothe highly acidic environment of the stomach and allows the maintenanceof therapeutic blood levels of the active ingredients over extendedperiods of time. Such degradation may include, but is not limited to:cleaving of the phytosterols from their fatty acid carriers, andalteration or degradation of the phytosterols themselves.

[0037] The extended release of the extract over the course of its travelthrough the duodenum and small intestine can be achieved by any of anumber of slow dissolution technologies. These include, but are notlimited to: microencapsulation of the extract in coatings of variablethickness, each with a different dissolution pattern; encapsulation ofthe extract within a material matrix that dissolves slowly in theneutral environment of the duodenum and small intestine; and binding ofthe extract with bioadhesives which adhere to the wall of the smallintestine, for the purpose of providing extended, targeted release.Controlled release systems are described, for example, in U.S. Pat. Nos.6,124,477; 5,783,212; 5,415,878; 5,225,212; 5,133,974; 4,695,467;4,610,870; 4,259,314; 4,309,404; 4,248,857; and 4,140,255, all of whichare incorporated herein by reference in their entirety.

[0038] A preferred capsule coating for use in the compositions of thisinvention is described in European Patent EP 0 974 345, to MW Encap Ltd.(incorporated herein by reference). This coating comprises a suitablecapsule material, such as gelatin or hydroxypropylmethylcellulose(HPMC), to which a solute, such as propan-1-ol, propan-2-ol, or anotheralcohol, is added to elevate the thermal gelation temperature of thecapsule material. A plasticizer such as propylene glycol may also beadded. A gelling agent comprising one or more gums (e.g., gellan gum)may also be used in the coating. Finally, a hydrating agent may beincluded to aid in solubilizing the gum, and the hydrating agent mayoptionally be sodium citrate. The coating is prepared by heating asolution of the capsule material and the solute, and optionally aplasticizer. The gelling agent and hydrating agent are heatedseparately. When both heated solutions reach the desired temperature,they are thoroughly mixed to form the coating.

[0039] The extended release system according to this invention maximizesthe release time of the extract in the small intestine. This has theeffect of maintaining therapeutic levels of the active ingredient in theblood for an extended length of time, eliminating the spike and collapsepattern associated with less sophisticated medication systems thatrelease their active ingredients more rapidly into the digestive system.The extended release system preferably allows a medication schedule ofone oral dosage per day. The currently recommended medication schedulefor standard saw palmetto extract compositions for the treatment of BPHis 160 milligrams (mg) of the extract twice a day: once in the morning,once in the evening. It is well-recognized that a once-a-day medicationschedule is far more likely to be followed by patients, and therefore ismore likely to be effective. Further, the saw palmetto extractcomposition with an extended release system according to this inventionmaintains a more even therapeutic level of the active ingredient in thebloodstream. Therefore, the preferred doses of the compositions of thisinvention include from about 50 mg to about 1 g of saw palmetto extract,and most preferably 320 mg.

[0040] Oral preparations of the saw palmetto extract useful in thepractice of this invention may be prepared as a plant oil, or an aqueousor organic extract of the whole plant or a selected part of the plant.According to one aspect of this invention, the extract is preferablyderived from the saw palmetto berry. The compositions of this inventioncan also utilize saw palmetto that has been processed in whole or inpart to form a powder. Extracts of the plant material (especially anoil) are presently preferred; however, powdered plant materials are alsowell-suited for oral applications where the drug is administered insolid form, e.g., tablets or capsules. In a preferred embodiment of thepresent invention, the saw palmetto extract is a solvent-free highpurity, high potency extract prepared using a supercritical carbondioxide extraction process. Such extraction processes are well known inthe art.

[0041] In addition to the saw palmetto extract, which contains theactive ingredients, the oral preparations of this invention may alsocontain appropriate tablet additives, including: diluents such ascalcium carbonate, magnesium carbonate, dicalcium phosphate or mixturesthereof; binders such as hydroxypropyl-methylcellulose,hydroxypropylcellulose, polyvinylpyrrolidone, pregelatinized starch orgum acacia or mixtures thereof; disintegrants such as cross-linkedpolyvinylpyrrolidone, sodium starch glycolate, croscarmellose sodium ormixtures thereof; lubricants, such as magnesium stearate or stearicacid, glidants; or flow aids, such as colloidal silica, talc or starch;and stabilizers, such as desiccating amorphous silica, coloring agents,and flavors.

[0042] The oral formulations according to the present invention arecontrolled or extended release formulations. The controlled releasesystem or extended release formulation according to this invention isbelieved to control the absorption of the phytosterols present in thesaw palmetto extract by coating it with a substance that retards releaseof the drug at certain pH values, while promoting disintegration and/orleaching of the drug at other pH values. The coating is designed toprevent premature disintegration of the capsule, tablet, or other oraldosage form in the acidic environment of the stomach, and to promoterelease of the drug in the intestine. A suitable controlled releasecapsule coating is one which will dissolve upon contacting intestinalfluids at higher pH levels (pH greater than 4.5), such as those foundwithin the duodenum and small intestine. The pH of the small intestinegradually increases from about 4.5 to about 6.5 in the duodenal bulb, toabout 7.2 in the distal portions of the small intestine (ileum). Inorder to provide predictable dissolution corresponding to the smallintestine transit time of about 3 hours to about 24 hours and permitreproducible release therein, the coating should begin to dissolvewithin the pH range of the duodenum and continue to dissolve at the pHrange within the small intestine. Therefore, the amount of controlledrelease capsule coating should be such that it is substantiallydissolved during the desired transit time within the duodenum and smallintestine. It should be noted that little absorption of the phytosterolsof the saw palmetto extract can occur after the composition enters thelarge intestine. As described above, a preferred controlled-releasecapsule formulation is set forth in European Patent EP 0 974 345, whichis incorporated herein by reference.

[0043] A preferred composition according to the present inventioncomprises a two-part hard shell capsule that encases a matrix holdingfrom about 50 mg to about 1 g saw palmetto extract. A more preferredcomposition comprises a two part hard shell capsule encasing a matrixholding about 320 mg of saw palmetto extract.

[0044] Enteric coatings may be provided as part of the oral dosageformulation. The enteric coating may be an essentially conventionalcoating material known for enteric coating, for example, entericpolymers such as cellulose acetate phthalate, cellulose acetatesuccinate, methylcellulose phthalate, ethylhydroxycellulose phthalate,polyvinylacetate phthalate, polyvinylbutyrate acetate, vinylacetate-maleic anhydride copolymer, styrene-maleic mono-ester copolymer,methyl acrylate-methacrylic acid copolymer, methacrylate-methacrylicacid-octyl acrylate copolymer, etc. These may be used either alone or incombination, or together with other polymers than those mentioned above.The enteric coating may also include insoluble substances which areneither decomposed nor solubilized in living bodies, for example, alkylcellulose derivatives such as ethyl cellulose, crosslinked polymers suchas styrene-divinylbenzene copolymer, polysaccharides having hydroxylgroups such as dextran, cellulose derivatives which are treated withbifunctional crosslinking agents such as epichlorohydrin,dichlorohydrin, 1,2,3,4-diepoxybutane, etc. The enteric coating may alsoinclude starch and/or dextrin. The enteric coating may also include ananti-tack agent such as talc, silica, or glyceryl monostearate. Theenteric coating can also contain other ingredients such as surfactants,pigments, and fillers. The enteric coating may be found on the oralformulations of this invention and may be formed as a single layer, oras multiple layers. If the coating includes multiple layers, thencompositions of the layers may be the same or different, and may be ofthe same or varying thicknesses. The controlled release system may alsoinclude providing an agent that acts to bind the saw palmetto extract tothe walls of the small intestine.

[0045] According to an additional aspect of this invention, thecontrolled-release saw palmetto extract formulation may be combined withan additional compound useful in treating spasms in smooth musclefibers. Such a compound would aid in treating BPH symptoms by minimizingbladder and urethral contractions that cause sudden urges to urinate.Antispasmodic compounds useful in minimizing such smooth musclecontractions include, but are not limited to: extracts or tinctures ofBelladonna alkaloid, Choleus Forskholi, European Goldenrod, Peppermint,and Passion Fruit seed.

[0046] It is envisioned that additional compounds may optionally beadministered along with the compositions of this invention, either byincluding the compounds in the composition, or by co-administering thecompound. Such compounds may include NSAIDS (e.g., ibuprofen, naproxinsodium), COX-2 inhibitors (e.g., celecoxib, refecoxib), and others.

[0047] The compositions of the present invention may optionally containa bioadhesive which allows adherence of the compositions to theintestinal mucosal thereby providing an additional means by which tocontrol the extended release characteristics of the compositions. Suchbioadhesives include but are not limited to polycarbophil containingbioadhesives and others such as those described in U.S. Pat. Nos.5,876,744; 5,474,768, and 4,615,697 all of which are incorporated hereinby reference in their entirety.

[0048] The following examples are intended to be illustrative of theinvention and are not intended to limit the invention as set out in theappended claims.

[0049] Example 1 describes an exemplary extended release formulation ofsaw palmetto extract. Example 2 describes an exemplary formulation ofsaw palmetto extract in combination with an antispasmodic compound.

EXAMPLE 1 Extended Release Formulation of Saw Palmetto Extract

[0050] A preferred extended release formulation of the present inventioncomprises a two-part hard shell capsule that encases a matrix(preferably a fatty matrix) that in turn comprises about 50 mg to about1 g of saw palmetto extract. Other suitable matrices are well known inthe art. Preferably, the formulation comprises about 320 mg of extract.Preferably, the shell comprises a material free of animal components. Apreferred saw palmetto extract is prepared by an extraction process thatis free of organic solvents and which provide a high-purity, highpotency saw palmetto oil. Such an extract may be prepared using a highpressure, supercritical carbon dioxide extraction process, by methodswell known in the art.

[0051] The capsule is formed from a material such as gelatin orhydroxypropylmethyl cellulose (HPMC), to which a solute, such aspropan-1-ol, propan-2-ol, or another alcohol, is added to elevate thethermal gelation temperature of the capsule material. A plasticizer suchas propylene glycol may also be added. A gelling agent comprising one ormore gums (e.g. gellan gum) may also be used in the coating. Finally, ahydrating agent may be included to aid in solubilizing the gum, and thehydrating agent may optionally be sodium citrate. The coating isprepared by heating a solution of the capsule material and the solute,and optionally a plasticizer. The gelling agent and hydrating agent areheated separately. When both heated solutions reach the desiredtemperature, they are thoroughly mixed to form the capsule, which isthen hardened to the desired shape as it cools. (See also EP 0 974 345,incorporated herein by reference).

[0052] The composition may also include a bioadhesive molecule whichallows adherence of the compositions to the intestinal wall. Suchbioadhesives include but are not limited to those described in U.S. Pat.Nos. 5,876,744; 5,474,768; and 4,615,697. See also Lehr et al., J. PharmPharmacal. 44:(1992) pp. 402-407 (incorporated herein by reference).

[0053] After the tablet is swallowed, the capsule goes through thestomach and into the upper intestine by which time the shell isdissolved and the matrix is exposed. The matrix comprising the same sawpalmetto extract first becomes available to the body in the upper(small) intestine and is released in the intestine over the next 8-10hours as the matrix traverses the small intestine releasing its extractbefore entry into the large intestine.

EXAMPLE 2 Formulation of Saw Palmetto Extract and Antispasmodic Compound

[0054] An additional formulation of the present invention comprises atwo-part hard shell capsule that encases a matrix that in turn comprisesabout 50 mg to about 1 g of saw palmetto extract. Preferably, the shellcomprises a material free of animal components. The dosage capsule alsocontained about 1 mg to about 1,000 mg of one or more antispasmodiccompounds, such as extracts or tinctures of Belladonna alkaloid, Choleusforskholi, European goldenrod, peppermint, and Passion Fruit seed. Thetablet is formed in the same manner described above with respect toExample 1, and allows extended release of the tablet contents duringtransit through the intestinal tract.

[0055] Thus, what has been described is a composition and method fortreating BPH and improving the effectiveness of therapies utilizing sawpalmetto extract. While the present invention has been described withrespect to what are presently considered to be the preferredembodiments, it is to be understood that the invention is not limited tothe disclosed embodiments. To the contrary, the invention is intended tocover various modifications and equivalent arrangements included withinthe spirit and scope of the appended claims. Therefore, the scope of thefollowing claims is to be accorded the broadest interpretation so as toencompass all such modifications and equivalents.

We claim:
 1. An oral composition for use in treating benign prostatichyperplasia, comprising: a saw palmetto extract; and a controlledrelease system, said system comprising: a coating formed from a materialimpervious to acidic conditions in the stomach that is soluble in theduodenum and small intestine.
 2. The composition of claim 1, wherein thecontrolled release system prevents the saw palmetto extract from beingdegraded in the stomach.
 3. The composition of claim 1, wherein thecontrolled release system comprises a system selected from the groupconsisting of microencapsulation in coatings of variable thickness, eachwith a different dissolution pattern; and capsulation in a materialmatrix that dissolves slowly in the neutral environment of the duodenumand small intestine; and binding with bioadhesives that adhere to thewall of the small intestine.
 4. The composition of claim 1, wherein thecomposition further comprises a compound that minimizes smooth musclecontractions.
 5. The composition of claim 4, wherein the compound thatminimizes smooth muscle contractions is an antispasmodic compoundselected from the group consisting of Belladonna Alkaloid, CholeusForskholi, European Goldenrod, Peppermint, and Passion Fruit seed.
 6. Anoral composition for improving the effectiveness of saw palmetto extracttherapy, comprising: a saw palmetto extract; and a controlled releasesystem, said system comprising: a coating formed from a materialimpervious to acidic conditions in the stomach that is soluble in theduodenum and small intestine.
 7. The composition of claim 6, wherein thecontrolled release system prevents the saw palmetto extract from beingdegraded in the stomach.
 8. The composition of claim 6, wherein thecontrolled release system comprises a system selected from the groupconsisting of microencapsulation in coatings of variable thickness, eachwith a different dissolution pattern; and capsulation in a materialmatrix that dissolves slowly in the neutral environment of the duodenumand small intestine; and binding with bioadhesives that adhere to thewall of the small intestine.
 9. The composition of claim 6, wherein thecomposition further comprises a compound that minimizes smooth musclecontractions.
 10. The composition of claim 9, wherein the compound thatminimizes smooth muscle contractions is an antispasmodic compoundselected from the group consisting of Belladonna Alkaloid, CholeusForskholi, European Goldenrod, Peppermint, and Passion Fruit seed. 11.An oral saw palmetto extract composition, the improvement comprising: acompound that reduces smooth muscle contractions; and a controlledrelease system, said system comprising: a system selected from the groupconsisting of microencapsulation in coatings of variable thickness, eachwith a different dissolution pattern; encapsulation in a material matrixthat dissolves slowly in the neutral environment of the duodenum andsmall intestine; and binding with bioadhesives that adhere to the wallof the small intestine.
 12. A method of treating benign prostatichyperplasia, comprising the step of: administering a therapeuticallyeffective amount of a saw palmetto extract which comprises an oraldelivery vehicle comprising a coating formed from a material imperviousto acidic conditions in the stomach that is soluble in the duodenum andsmall intestine.
 13. The method of claim 12, wherein the saw palmettoextract is released into the bloodstream over an extended period. 14.The method of claim 12, wherein the coating provides controlled releaseof the saw palmetto extract by a method selected from the groupconsisting of microencapsulation in coatings of variable thickness, eachwith a different dissolution pattern; and capsulation in a materialmatrix that dissolves slowly in the neutral environment of the duodenumand small intestine; and binding with bioadhesives that adhere to thewall of the small intestine.
 15. The method of claim 12, wherein thecoating passes through the stomach intact.
 16. The method of claim 12,wherein the saw palmetto extract is initially released in the duodenum.17. The method of claim 12, wherein the saw palmetto extract is releasedbefore it enters the colon.
 18. A method of improving the efficacy ofsaw palmetto extract treatment, comprising the steps of: providing atherapeutically effective amount of a saw palmetto extract in an oralformulation; and encapsulating the saw palmetto extract in a coatingformed from a material impervious to acidic conditions in the stomachthat is soluble in the duodenum and small intestine.
 19. The method ofclaim 18, wherein the saw palmetto extract is released into thebloodstream over an extended period.
 20. The method of claim 18, whereinthe coating provides controlled release of the saw palmetto extract by amethod selected from the group consisting of microencapsulation incoatings of variable thickness, each with a different dissolutionpattern; and capsulation in a material matrix that dissolves slowly inthe neutral environment of the duodenum and small intestine; and bindingwith bioadhesives that adhere to the wall of the small intestine. 21.The method of claim 18, wherein the coating passes through the stomachintact.
 22. The method of claim 18, wherein the saw palmetto extract isinitially released in the duodenum.
 23. The method of claim 18, whereinthe saw palmetto extract is released before it enters the colon.
 24. Acomposition for use in treating benign prostatic hyperplasia comprising:a saw palmetto extract provided in an oral formulation; and one or moreantispasmodic compounds selected from the group consisting of BelladonnaAlkaloid, Choleus Forskholi, European Goldenrod, Peppermint, and PassionFruit seed.
 25. The composition of claim 24, further comprising acontrolled release system, comprising: a coating formed from a materialimpervious to acidic conditions in the stomach that is soluble in theduodenum and small intestine.
 26. A method for improving the efficacy ofsaw palmetto extract treatment, comprising the steps of: providing atherapeutically effective amount of a saw palmetto extract; and furtherproviding one or more antispasmodic compounds.
 27. The method of claim26 wherein the antispasmodic compound is selected from the groupconsisting of Belladonna Alkaloid, Choleus Forskholi, EuropeanGoldenrod, Peppermint, and Passion Fruit seed.